Expert citations
- CPP is divided into idiopathic and secondary CPP based on etiology. The causes of secondary CPP are diverse, and the most common cause of secondary CPP in young children is hypothalamic hamartoma.
- GnRHa is the first choice for secondary CPP caused by hypothalamic hamartoma if it cannot be surgically treated, and multiple studies have confirmed that GnRHa treatment can well control CPP caused by hypothalamic hamartoma.
Precocious puberty in children has become a pediatric endocrine disease with a high incidence, and the most common form of precocious puberty is central precocious puberty (CPP), which can be divided into idiopathic CPP and secondary CPP according to the etiology, and the causes of secondary CPP are diverse, and determining the cause of CPP will have a positive impact on the prevention, early and accurate diagnosis and better prognosis of CPP in children.
On June 1-4, 2024, the latest ENDO (American Endocrine Society) annual meeting held in Boston reported for the first time a case report on hypothalamic teratoma complicated by CPP.
Expert Profile
Prof. Di Wu
- Chief Physician, Doctor of Medicine, Associate Professor, Master's Supervisor
- Deputy Director, Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Children's Medical Center
- Co-director of the Birth Defect Genetics Research Office of Beijing Institute of Pediatrics
- He is a member of the Diabetes Branch of the Chinese Medical Association
- Member of the Rare Disease Group of the Pediatric Branch of the Chinese Medical Association
- Member of the Standing Committee of the Diabetes Branch of the Beijing Medical Association
- He is a member of the Education and Management Group of the Diabetes Branch of the Chinese Medical Association
- He is an editorial board member of the Chinese Journal of Diabetes, the International Journal of Endocrinology and Metabolism, the Chinese Journal of Pediatrics Newsletter, and the Chinese edition of ESJ Pediatrics
- In 2014, he went to Morgan Stanley Presbyterian Children's Hospital in New York, USA for further study
- From 2017 to 2018, he was a visiting scholar of the China Scholarship Council at Boston Children's Hospital, Harvard Medical School
1. The latest case report of the ENDO 2024 conference - GnRHa in the treatment of secondary CPP complicated by hypothalamic teratoma
Case information is shown in Table 1.
Table 1 Case information[1]:
Treatment Procedure:
Dosing regimen: GnRHa 30mg*, once every 3 months. The parameters for post-treatment laboratory evaluation are shown in Table 2.
Table 2 Laboratory evaluation parameters after GnRHa treatment
Recommendations for further processing: Surgical intervention is not recommended given that GnRHa injections every 3 months may be effective, there are no central nervous system symptoms associated with teratomas, and there are no changes in MRI imaging.
As the first reported case of hypothalamic teratoma complicated by CPP in a male child, the patient responded well to GnRHa therapy, although the cause was rare. In general, the CPP caused by central nervous system abnormalities in the above cases is secondary CPP, although there are not many reports in the literature, but as a category of many causes of CPP, it also deserves our attention in clinical practice.
2. Common causes and treatment of secondary CPP
1. A common cause of secondary CPP - hypothalamic hamartoma
Understanding the causes of CPP helps us understand the underlying mechanisms of normal and abnormal puberty development and enable us to choose the appropriate treatment. CPP is further divided into idiopathic CPP (ICPP) and secondary CPP based on the cause of the disease [2] (table 3).
Table 3 Classification and etiology of CPP
Secondary CPP is 3.5 times more common in boys than in girls. Underlying central nervous system pathology is detected in approximately one fifth of boys with CPP [3].
This is the first case report of hypothalamic teratoma complicated by CPP in a male, which is very rare. Among young children's secondary CPP, the most common cause is hypothalamic hamartoma (HH). HH has a unique clinical presentation, with most cases occurring in early childhood, with CPP being the most common presenting symptom of HH [4]. Authors report that 80 percent of patients with hypothalamic hamartomas have a diagnosis of CPP [4]. HH-associated CPP occurs earlier than idiopathic CPP, with a mean age of onset of 3.7 years in males and 2.5 years in females [5]. Breast development, menarche, or penis enlargement in men and young children are manifested by breast development, menarche, and penile enlargement, pubic hair, acne, a thickened voice, muscular development, and an adolescent personality [6].
In addition to HH, tumors with endocrine function or other space-occupying lesions can cause or be complicated by CPP [6]. These include myelomeningocele, hydrocephalus, encephalitis, neonatal hypoxic-ischemic encephalopathy, and neurofibromatosis type 1, which are significantly more common in boys than girls [4].
2. GnRHa treatment can control CPP caused by hypothalamic hamartoma
Early studies of HH treatment have shown that the vast majority of HH-induced CPP symptoms can be clinically cured by surgical treatment. However, surgery is invasive, and some hamartomas are not suitable for surgery due to factors such as tumor size and location. With the increasing number of studies on long-term follow-up of children with pharmacological precocious puberty, GnRHa has become the first-line treatment for CPP [7]. At present, simple precocious puberty due to HH is the preferred treatment for GnRHa in the absence of surgery [7].
As a standard drug for children with CPP, GnRHa can effectively control the sexual development process of children with CPP, delay skeletal maturation, improve final adult height (FAH), and avoid psychological and behavioral problems [8]. In addition to the case report in this case report, children with CPP due to hypothalamic teratomas may be effective with GnRHa alone, and multiple studies have demonstrated that GnRHa therapy is effective in controlling HH-induced CPP (Table 4).
Table 4 Study of CPP caused by hypothalamic hamartoma treated with GnRHa
【Experts' Conclusion】
The etiology of secondary CPP is diverse, and the differential diagnosis of the etiology is crucial, and the most common cause of secondary CPP in young children is HH. At present, it is advocated that GnRHa treatment is the first choice for children with simple precocious puberty caused by HH, and studies have confirmed that GnRHa treatment can effectively control HH-induced CPP. However, most of the GnRHa used in the current study are in the 1-month dosage form, and the long-acting dosage form of GnRHa is expected to play a greater role in the treatment of CPP due to the relatively long treatment process of CPP, which usually takes 2 years or more. The long-acting formulation of GnRHa can greatly reduce the number of injections, and the longer injection interval can also improve the convenience and compliance of treatment for children with CPP. Based on the initial success of GnRHa in the treatment of HH-induced CPP, we have reason to believe that the genetic discovery involving the etiology of CPP will lay the foundation for the treatment of potential new targets of specific CPP, and there will be better treatment methods to bring good news to children with CPP in the future!
*The 3-month dosage form of triptorelin is approved in China for the treatment of central precocious puberty at a specification of 15 mg
bibliography
1.SAT-128 / SAT-128 - CPP with Rapid Pubertal Progression in a 9-Year-Old Boy with Hypothalamic Teratoma.Session P06 - Pediatric Endocrinology: Puberty
2. Yu Jian, Sun Wen, Sun Yanyan. Guidelines for the diagnosis and treatment of children with precocious puberty with integrated traditional Chinese and Western medicine (2023 edition)[J].Journal of Traditional Chinese Medicine,2024,65(05):546-552.)
3.Vurallı D, Özön A, Gönç EN, Oğuz KK, Kandemir N, Alikaşifoğlu A. Gender-related differences in etiology of organic central precocious puberty. Turkish J Pediatr. 2020; 62(5):763-769.
4.Suh J, Choi Y, Oh JS, Song K, Choi HS, Kwon A, Chae HW, Kim HS. Management of Central Precocious Puberty in Children with Hypothalamic Hamartoma. Children (Basel). 2021 Aug 18; 8(8):711.
5.Brito VN, Canton APM, Seraphim CE. The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty. Endocr Rev. 2023 Mar 4; 44(2):193-221.
6. Luo Shiqi, Li Chunde, Ma Zhenyu, et al. Clinical analysis of 40 cases of hypothalamic hamartoma[J] . Chinese Journal of Neurosurgery, 2002, 18(01) : 37-40.
7. Li Ping, Zhao Rui. New progress in the clinical treatment of hypothalamic hamartoma [J] . Chinese Journal of Neurosurgery, 2021, 37(2) : 206-209.
8. Endocrinology, Genetics and Metabolism Group, Chinese Society of Pediatrics, Editorial Committee of Chinese Journal of Pediatrics. Expert consensus on the diagnosis and treatment of central precocious puberty(2022)[J].Chinese Journal of Pediatrics,2023,61(01):16-22.)
9.Jaruratanasirikul S, Thaiwong M. Outcome of gonadotropin-releasing analog treatment for children with central precocious puberty: 15-year experience in southern Thailand. J Pediatr Endocrinol Metab. 2011; 24(7-8):519-23.
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